Factors Influencing Left Ventricular Ejection Fraction in patients with CMVD and OCAD

Objective: The aim of our research was to evaluate the relationship involving LVEF, LDL, BNP, Troponin I and CFR, and to determine the predictors of LVEF in patients with CMVD and OCAD, and in patients with CMVD. Results: The mean age was 58.5±12.5 years. Approximately 60% of the patients were women. Chest pain was the common symptom in both conditions around 45% followed by chest tightness which was 25%. In patients OCAD and CMVD we found low density lipoprotein-c (LDL-c) had significant inverse relationship with LVEF (r= -0.323, P= 0.042), LVEF also had significant negative relationship with BNP, and Troponin-I. While a significant direct relationship turned out to be observed linking LVEF with CFR (r= 0.422, P=0.007). Left ventricular ejection fraction had significant negative relationship with LDL-C (r= -0.489, P=0.029), and BNP (r= -0.472, P=0.035) in patients with OCAD only. Age, blood pressure, lipid levels, RDW, HbA1C, symptoms, NYHA classification, Alcohol drinking, hypertension, diabetes mellitus, troponin levels and BNP were the predictors for LVEF in CMVD patients. We depicted a strong negative relationship between LVEF and biomarkers (LDL-c, BNP, Troponin-I), with a significant positive association between LVEF and CFR. BNP, Troponin-I and CFR. We conducted correlation tests using Spearman’s rho to assess the relationship between LVEF, LDL-C, BNP, Troponin-I and CFR in patients with CMVD and OCAD (Fig. 1A, B, C and D). Low density lipoprotein-c (LDL-c) had significant inverse relationship with LVEF (r= -0.323, P = 0.042), LVEF also had significant negative relationship with BNP (r= -0.562, P < .0001), and troponin-I (r= -0.311, P = 0.04). While a significant positive relationship was observed between LVEF and CFR (r = 0.422, P = 0.007).


Introduction
Coronary artery disease is a major non communicable disease problem around the world.
The coronary vessels damage can be caused by an array of crucial risk factors such as hypertension, dyslipidemia, diabetes mellitus and smoking cigarettes [1]. Furthermore, obstructive coronary artery disease occurs less frequently in females, preceding studies revealed a poor prognosis in females in relation to male counterparts amid patients exhibiting with symptoms of stable angina [2]. Even though there is detailed documentation and guidelines emphasizing administration of secondary prevention medication, an under usage of these medication was observed, meaning that many patients with coronary artery disease did not attain the treatment objective for secondary prevention [3]. Epidemiology studies have revealed men to be more affected by OCAD compared to women. Moreover, female patients are believed to have more symptom burden and a higher rate of functional disability but a lower prevalence of OCAD, they usually present with NOCAD particularly CMVD. In patients with CAD, men tend to have a higher lipid core compared with women [4].
Previous studies were done to investigate serum total cholesterol in relation to LVEF and Coronary artery disease where they found out higher total cholesterol and HDL-C are associated with higher LVEF [5,6]. There were no studies done in evaluating the LDL-c, BNP, Troponin-I and CFR in association with LVEF in patients with OCAD and CMVD.
In our study, we used a prospective clinical observational design to investigate the association between LVEF and LDL-c, BNP, Troponin-I, and CFR and to determine the predictors of LVEF

Patients Demographic and clinical characteristics
Forty patients participated in our study, whereby twenty patients had coronary microvascular dysfunction (CMVD) and twenty patients had obstructive coronary artery disease (OCAD). The mean age was 58.5 ± 12.5 years. Approximately 60% of the patients were women. The mean left ventricular ejection fraction was 56.7 ± 7.9, and the mean coronary flow reserve was 2.04 ± 0.56 respectively. The patient's demographic and clinical characteristics are summarized in Table 1. 136.6 ± 20.9 Diastolic BP in mmHg, (mean ± SD) 82.6 ± 16.6 LDL-C in µmol/l, (mean ± SD) 3.5 ± 1.6 HDL-C in µmol/l, (mean ± SD) 1. 16 (Table 2).

Discussion
The current research indicated a negative correlation between LVEF and LDL-c, BNP and Troponin-I in patients with OCAD and CMVD. To the best our knowledge, this is the first research to reveal the relationship between LVEF and biomarkers (LDL-C, BNP and Troponin-I). We also found out a positive association between LVEF and CFR in patients with OCAD AND CMVD. This finding was congruent with our previous study, whereby there was a positive correlation between LVEF and CFR [8].
Previous studies have shown that hyperlipidemia adversely influenced the left ventricular ejection fraction, particularly in patients with myocardial infarction. They went further and detailed an important positive correlation between left ventricular ejection fraction and high density lipoproteincholesterol, suggesting that HDL-cholesterol might influence left ventricular systolic function through extra-atherosclerotic mechanisms because they observed left ventricular ejection fraction was adversely influenced by dyslipidemia irrespective of the severity of coronary atherosclerosis [9,10,11]. There was another study in which, they investigated the association between lipid profile levels and right ventricular volume overload in congestive heart failure, where they revealed lipid levels (total cholesterol, triglycerides, low density lipoprotein-c, and high density lipoprotein-c) were inversely correlated to right ventricular end diastolic diameter and right atrium [12]. In our study, which involved patients with obstructive coronary artery disease and coronary microvascular dysfunction, we found out LDL-c to be inversely correlated with left ventricular ejection fraction and it was statistically significant. Meaning one-unit change increase in LDL-c is associated with a unit decrease in LVEF percentage. This show our study concur with previous study findings.
Several studies have revealed a negative correlation between BNP and left ventricular ejection fraction. They revealed that BNP levels were low in patients with heart failure with preserved ejection fraction compared to patients with heart failure with reduced ejection fraction. In another study, they also discovered an important correlation between NT-proBNP and LVEF in elderly patients, whereby worsening LVEF had a significant correlation with NT-proBNP levels [13,14]. In our study, we also found a negative correlation between left ventricular ejection fraction and B-type natriuretic peptide in patients with obstructive coronary artery disease and coronary microvascular dysfunction (r= -0.562, P < .0001) and in patients with OCAD alone (r= -0.472, P = 0.035), meaning that one unit change increase in BNP was related with a unit decrease in LVEF percentage.
Furthermore, another biomarker troponin-I is a power indicator of myocardial necrosis, it has been studied before and was found to be inversely correlated with left ventricular ejection fraction especially in patients after first myocardial infarction. They found out that the left ventricular ejection fraction of < 50% was predicted by troponin I concentration of ›6.6 ng/ml. In another research analysis, it showed that patients with severe left ventricular systolic dysfunction (LVEF < 35%) had the highest level of troponin I and vice versa. They also showed that the LVEF had a negative correlation with troponin I levels (r= -0.54, P = 0.001). Despite the above fact, there was an exploration of troponin T, whereby it was also revealed that there was a negative correlation between troponin T levels and LVEF (r= -0.72, P = < .0001) [15,16,17]. In our findings, we showed that there was a significant negative relationship between troponin I and left ventricular ejection fraction in patients with OCAD and CMVD (r= -0.311, P = 0.04). Meaning one-unit change increase in troponin I levels was associated with a unit decrease in LVEF percentage.
Form our study, we discovered the importance of these biomarkers (LDL-c, BNP, and Troponin-I) as prognostic indicators for patients with OCAD and CMVD.
Moreover, there were studies done in the area of determination of predictors of LVEF. Whereby, their analysis demonstrated that several traditional and easily available factors were associated with a greater risk of heart failure development, even among low-risk CAD population. Some of the studies showed lipids predicted the severity of new onset CAD in type-2 DM patients and not in relation to LVEF, differentiating from our study. In another research, low HDL-c was strongly predictive of cardiovascular events in patients with coronary artery disease [18, 19, and 20]. In our research we also found out that traditional risk factors influenced the LVEF concurring the previous studies even though we were the only one, who further evaluated patients with OCAD and CMVD. In the current published articles indicated the relevance of inflammatory biomarkers particularly CRP and Pentraxin 3 as the prognostic indicators of coronary artery disease congruent with our findings even though we assessed different biomarkers (LDL-c, BNP, troponin-I) [21,22].
We believe by sharing these findings of our study, will empower the clinicians with knowledge on coronary microvascular dysfunction in relation to OCAD, by exploring the relationship between LVEF and biomarkers, and predictors of LVEF in these patients.

Conclusion
There was a strong negative relationship between LVEF and biomarkers (LDL-c, BNP, Troponin-I), with a significant positive association between LVEF and CFR. Traditional risk factors were the predictors of LVEF in OCAD and CMVD patients.
Limitation a small sample size was our study limitation Declarations Ethical approval and consent to participate: The clinical protocol and the informed consent forms were approved by the ethics committee of and Troponin I (pg/ml)